目的 探讨血清乳酸脱氢酶(LDH)在中晚期肝癌患者接受靶向联合免疫治疗后的预后预测价值。方法 选取2022年1月—2024年8月在莆田学院附属医院肿瘤内科经病理和影像学检查确诊的中晚期肝癌患者作为研究对象。从医院的电子病历系统中收集患者的基线资料,随访截止2025年8月,并记录随访结果,包括患者的疾病缓解情况和死亡情况,以及无疾病进展生存期(PFS)、总生存期(OS)。采用Kaplan-Meier方法绘制不同基线LDH水平患者的OS生存曲线,并通过Log-rank检验比较生存曲线。同时,运用多因素Cox比例风险回归分析探讨影响中晚期肝癌患者在接受靶向联合免疫治疗后OS的相关因素。结果 结果显示,在50例肝癌患者中,基线LDH低于200 U/L的有15例,而高于200 U/L的有35例。与基线LDH<200 U/L组相比,基线 LDH≥200 U/L患者PFS、OS更短,差异均有统计学意义(χ2分别为5.51、15.6,P值分别为0.019、0.017)。治疗8周后,与LDH降低患者相比,LDH升高患者OS更短,差异有统计学意义(χ2=13.2,P=0.04)。多因素Cox比例风险回归分析结果表明,基线LDH水平超过200 U/L是中晚期肝癌患者接受靶向联合免疫治疗后OS的影响因素[P=0.035,HR(95%CI)=5.03(1.12,22.54)]。结论 基线LDH水平较低的患者表现出更好的OS。基线LDH水平可以作为预测中晚期肝癌患者在接受靶向联合免疫治疗时预后的指标。
Objective To evaluate the prognostic significance of serum lactate dehydrogenase(LDH)levels in patients with advanced hepatocellular carcinoma(HCC)undergoing targeted therapy combined immunotherapy.Methods Patients diagnosed with advanced HCC were selected in Putian College Affiliated Hospital from January 2022 to August 2024,diagnosed with pathological and imaging examinations results.Patient baseline data were collected from the hospital’s electronic medical records,with follow-up extending until August 2025.We documented outcomes such as disease response and mortality,along with progression-free survival(PFS)and overall survival(OS).Kaplan-Meier survival curves were constructed based on baseline LDH levels,and the Log-rank test was employed for comparison.Additionally,multivariate Cox proportional hazards regression analysis was conducted to identify factors influencing OS in patients receiving targeted therapy combined immunotherapy.Results Among the 50 patients,15 had baseline LDH levels below 200 U/L,while 35 had levels above.Patients with baseline LDH≥200 U/L had significantly shorter PFS and OS than those with baseline LDH <200 U/L(χ2=5.51 and 15.6 for PFS and OS,respectively;P=0.019 and 0.017,respectively).After 8 weeks of treatment,patients with increased LDH had significantly shorter OS compared with patients with decreased LDH(χ2=13.2,P=0.04).Multivariate Cox proportional hazards regression analysis indicated that a baseline LDH level exceeding 200 U/L is an independent prognostic factor for OS in patients with intermediate to advanced HCC receiving targeted therapy combined with immunotherapy(P=0.035,HR 5.03[1.12,22.54]).Conclusions Patients with lower baseline LDH levels demonstrated better OS,suggesting that baseline LDH can serve as an important prognostic indicator for advanced HCC patients undergoing targeted combined immunotherapy.
实体瘤对免疫治疗应答非常有限,因此,如何有效提升肿瘤免疫治疗的疗效,已成为当前肿瘤免疫治疗领域亟待解决的关键难题与挑战。髓系来源抑制性细胞(MDSCs)的趋化募集及其所介导的肿瘤免疫逃逸机制,是制约实体瘤免疫治疗效果的核心因素之一。文章深入探讨了MDSCs的起源、表型特征、其介导肿瘤免疫逃逸的具体机制,以及当前针对MDSCs的靶向治疗策略与将MDSCs靶向疗法与肿瘤免疫治疗相结合的最新研究进展。此外,文章还系统性地分析了靶向MDSCs联合免疫治疗策略所面临的关键挑战,并据此提出了MDSCs的精准靶向策略。这一策略旨在精确激活抗肿瘤免疫反应,为癌症患者提供更为个性化、高效的治疗方案,从而开启肿瘤免疫治疗领域的新纪元,为癌症治疗策略的创新与发展贡献力量。
Solid tumors exhibit a very limited response to immunotherapy.Consequently,effectively enhancing the therapeutic efficacy of tumor immunotherapy has emerged as a critical challenge and problem that urgently needs to be addressed in tumor immunotherapy.The chemotaxis and recruitment of myeloid-derived suppressor cells(MDSCs)and the tumor immune evasion mechanisms mediated by them are one of the core factors that significantly restrict the efficacy of immunotherapy for solid tumors.In this review,we discuss the origins and phenotypic characteristics of MDSCs,the specific mechanisms by which they mediate tumor immune evasion,as well as current targeted therapeutic strategies for MDSCs and the latest research progress in combining MDSC-targeted therapy with tumor immunotherapy.Furthermore,we have systematically analyzed the key challenges faced by the combination of MDSC-targeted and immunotherapy strategies,and accordingly proposed a precise targeting strategy for MDSCs.This strategy aims to precisely activate anti-tumor immune responses,providing more personalized and efficient treatment options for cancer patients,thereby opening a new era in tumor immunotherapy and contributing to the innovation and development of cancer treatment strategies.
目的 探讨免疫治疗联合化学治疗(化疗)对晚期非小细胞肺癌(NSCLC)患者淋巴免疫及生活质量的影响,为临床进一步治疗提供参考。方法 选择2021年6月—2023年6月天津市滨海新区大港医院收治的晚期NSCLC患者120例进行研究,按抽签法分为干预组及对照组,每组60例,对照组采取单纯化疗方案,干预组采取免疫联合化疗方案,对比两组临床疗效、药物不良反应,治疗前后免疫功能(CD3+、CD4+、CD8+)、糖类抗原199(CA199)、糖类抗原 125(CA125)、血清癌胚抗原(CEA)水平及健康状态调查表(QOL)评分。结果 干预组患者治疗总有效率高于对照组(68.33%>41.67%,P<0.05);治疗后干预组患者CD3+、CD4+比例高于治疗前及对照组治疗后,CD8+比例低于治疗前及对照组治疗后(P<0.05);治疗后干预组血清CA199、CA125、CEA水平均低于治疗前及对照组治疗后(P<0.05);干预组药物不良反应发生率为16.67%,对照组为36.67%,干预组低于对照组(P<0.05);治疗后干预组QOL各维度评分高于对照组及治疗前(P<0.05)。结论 与单纯化疗相比,免疫联合化疗治疗晚期NSCLC患者,能有效降低肿瘤标志物水平,改善患者免疫指标,减轻药物不良反应,提高患者疗效及生活质量。
Objective To explore the effect of immunotherapy combined with chemotherapy on lymphatic immunity and quality of life of patients with advanced non-small cell lung cancer(NSCLC),and to provide reference for further clinical treatment. Methods A total of 120 patients with NSCLC from June 2021 to June 2023 were selected and divided into observation group and control group evenly according to the method of drawing lots,control group was treated with chemotherapy,the observation group was treated with immunotherapy combined with chemotherapy,and the clinical efficacy and adverse drug reactions were compared between the two groups.Before and after treatment,immune function(CD3+,CD4+,CD8+),carbohydrate antigen 199(CA199),carbohydrate antigen 125(CA125),serum carcinoembryonic antigen(CEA)levels and health status questionnaire(QOL-RRB- scores)were measured.Results The total effective rate in the observation group was significantly higher than that in the control group(68.33%>41.67%,P<0.05).After treatment,the ratios of CD3+ and CD4+ in the observation group were significantly higher than those before treatment and control group after treatment,and the ratio of CD8+ was significantly lower than that before and after treatment in the control group(P<0.05).After treatment,the serum levels of CA199,CA125 and CEA in the observation group were lower than those before and after treatment in the control group(P<0.05).The incidence of adverse drug reactions was 16.67% in the observation group and 36.67% in the control group,which was significantly lower in the observation group than in the control group(P<0.05).After treatment,the QOL scores in the observation group were significantly higher than those in the control group and before treatment(P<0.05).Conclusions Compared with chemotherapy alone,immunotherapy combined with chemotherapy can effectively reduce the levels of tumor markers,improve the immune indexes of patients,reduce the adverse drug reactions,and improve the efficacy and quality of life of patients with advanced NSCLC.
目的 观察程序性死亡受体1(PD-1)联合细胞毒性T淋巴细胞相关蛋白4(CTLA-4)双免疫疗法对改善晚期乳腺癌近期疗效及远期预后的影响。方法 选择2020年5月—2022年5月商丘市第一人民医院收治的124例晚期乳腺癌患者为研究对象,经随机数字表法将其分为对照组(60例)和观察组(64例),对照组予以常规PD-1单抗免疫疗法治疗,观察组采用PD-1联合CTLA-4双免疫疗法治疗,比较2组患者治疗前后肿瘤标志物水平、治疗后病灶缓解情况,对所有患者开展为期1年随访,统计并对比2组的不良反应发生情况及远期生存情况。结果 治疗前,2组患者的肿瘤标志物水平比较差异均无统计学意义(均P>0.05);治疗后,观察组的癌胚抗原为(3.36±0.17)ng/mL,糖类抗原15-3为(25.33±5.28)U/mL,糖类抗原19-9为(38.77±5.62)U/mL,均低于对照组[(5.27±1.36)ng/mL、(28.44±5.18)U/mL、(41.25±5.46)U/mL,均P<0.05]。治疗后,观察组的完全缓解率为21.88%(14/64),部分缓解率为31.25%(20/64),病情稳定率为37.50%(24/64),均高于对照组[8.33%(5/60)、13.33%(8/60)、23.33%(14/60)],肿瘤生长率为(30.27±5.18)%,肿瘤超进展率为6.25%(4/64),均低于对照组[(33.49±5.32)%、18.33%(11/60),均P<0.05]。治疗后,观察组的不良反应发生率为34.38%(22/64),略高于对照组33.33%(20/60),组间比较差异无统计学意义(P>0.05);观察组的中位无进展生存期为(9.33±2.25)月,中位总生存期为(10.76±3.32)月,均高于对照组[(7.25±2.31)月、(7.41±1.62)月,均P<0.05]。结论 PD-1联合CTLA-4双免疫疗法能有效改善晚期乳腺癌的近期疗效及远期预后,此疗法未明显增加不良反应发生风险,安全性高。
Objective To observe the effect of programmed cell death protein-1(PD-1)combined with cytotoxic T lymphocyte-associated antigen-4(CTLA-4)dual immunotherapy on the short-term efficacy and long-term prognosis of advanced breast cancer.Methods A total of 124 patients with advanced breast cancer who were admitted to the First People's Hospital of Shangqiu City from May 2020 to May 2022 were selected as the research objects.They were randomly divided into the control group(60 cases)and the observation group(64 cases)by the method of random number table.The control group was treated with conventional PD-1 monoclonal antibody immunotherapy,and the observation group was treated with PD-1 combined with CTLA-4 double immunotherapy.The levels of tumor markers before and after treatment and the focal remission after treatment were compared between the two groups.All patients were followed up for one year,the incidence of adverse reactions and long-term survival between the two groups were compared.Results Before treatment,there was no statistically significant difference in the levels of tumor markers between two groups(all P>0.05).After treatment,the carcino-embryonic antigen content of the observation group was(3.36±0.17)ng/mL,CA153 was(25.33±5.28)U/mL,and CA199 was(38.77±5.62)U/mL,which were lower than those of the control group [(5.27±1.36)ng/mL,(28.44±5.18)U/mL,(41.25±5.46)U/mL,all P<0.05].After treatment,the complete remission rate of the observation group was 21.88%(14/64),partial remission rate was 31.25%(20/64),and stable disease rate was 37.50%(24/64),all higher than those of the control group [8.33%(5/60),13.33%(8/60),23.33%(14/60)];tumor growth rate of the observation group was(30.27±5.18)%,hyper progressive disease rate was 6.25%(4/64),both lower than those of the control group [(33.49±5.32)%,18.33%(11/60),both P<0.05].After treatment,the incidence of adverse reactions in the observation group was 34.38%(22/64),slightly higher than that in the control group 33.33%(20/60)(P>0.05).The median progression free survival of the observation group was(9.33±2.25)months,and the median overall survival was(10.76±3.32)months,both higher than those of the control group [(7.25±2.31)months and(7.41±1.62)months](P<0.05).Conclusions PD-1 combined with CTLA-4 dual immunotherapy can effectively improve the short-term efficacy and long-term prognosis of advanced breast cancer.This therapy does not significantly increase the risk of side effects,which is safe.
目的 了解非结核分枝杆菌(nontuberculous mycobacteria,NTM)肺病患者免疫功能低下发生率,以及免疫支持的应用状况、探讨免疫支持治疗对患者2月末痰菌阴转及病变吸收的影响,为临床实施免疫干预提供参考依据。方法 分析广州市胸科医院2014年1月—2015年12月确诊的资料完整的381例NTM肺病患者免疫功能情况以及免疫支持的应用状况,观察组(加用免疫调节剂母牛分枝杆菌菌苗)228例与同期对照组(未使用免疫调节剂)153例进行2月末痰菌阴转及病变吸收情况比较。结果 381例患者中,免疫功能低下的发生率为45.67% (174/381);免疫支持率为59.84% (228/381)。细菌学改变:治疗前所有患者痰抗酸杆菌涂片和培养均为阳性。治疗2个月后两组的阴转率分别为67/228(29.38%)、17/153(11.11%),χ2=17.79,P<0.05。 影像学改变:两组的病变吸收有效率分别为62/228(27.19%)、16/153(10.45%),χ2=15.75,P<0.05;空洞吸收有效率分别为61/228(26.75%)、15/153(9.80%),χ2 =20.42,P<0.05。结论 非结核分枝杆菌肺病患者存在较高比例的免疫功能低下风险,观察组的痰茵阴转、病灶吸收和空洞闭合的疗效高于对照组。
Objective To explore the immune status of patients with nontuberculous mycobacterial(NTM) pulmonary disease, and the application of immunotherapy. to evaluate the influence of immunotherapy on sputum negative conversion and lesion absorption at the end of two months. provide reference data for immunotherapy. Methods The immune function and immunotherapy of 381 patients diagnosed as NTM pulmonary disease were retrospectively analyzed from January 2014 to December 2015 in Guangzhou Chest Hospital. Curative group (treated with antitubercular agents and immunomodulator mycobacterium vaccae) were compared with control group(treated with antitubercular agents alone) in sputum negative conversion and lesion absorption at the end of two month treatment. Results Of the 381 cases,45.67%(174/381)of the patients were immunocompromised, 59.84% (228/381)received immunotherapy. Bacteriologic changes: Both sputum smear and sputum culture were positive in all patents before treatment. after two months treatment, negative conversion in two groups were 67/228(29.38%),17/153(11.11%),χ2=17.79,P<0.05. 3. Radiological change: The rate of lesion absorption in curative group and control group were respectively 62/228(27.19%),16/153(10.45%),χ2=15.75,P<0.05;The rate of promoting cavity closure were respectively 61/228(26.75%),15/153(9.80%),χ2=20.42,P<0.05. Conclusion The immune function of NTM pulmonary disease had high ratio of being compromised. Curative group showed a significant effect of sputum negative conversion, lesion absorption and promoting cavity closure compared to the control group. Added to chemotherapy, M. vaccae is helpful in the treatment of nevertreated TB patients in terms of improving both Immunotherapy with M. vaccae had a beneficial influence on sputum negative conversion and X-ray appearances.
目的 探讨免疫治疗联合化学治疗(化疗)对晚期非小细胞肺癌(NSCLC)患者淋巴免疫及生活质量的影响,为临床进一步治疗提供参考。方法 选择2021年6月—2023年6月天津市滨海新区大港医院收治的晚期NSCLC患者120例进行研究,按抽签法分为干预组及对照组,每组60例,对照组采取单纯化疗方案,干预组采取免疫联合化疗方案,对比两组临床疗效、药物不良反应,治疗前后免疫功能(CD3+ 、CD4+ 、CD8+ )、糖类抗原199(CA199)、糖类抗原 125(CA125)、血清癌胚抗原(CEA)水平及健康状态调查表(QOL)评分。结果 干预组患者治疗总有效率高于对照组(68.33%>41.67%,P<0.05);治疗后干预组患者CD3+ 、CD4+ 比例高于治疗前及对照组治疗后,CD8+ 比例低于治疗前及对照组治疗后(P<0.05);治疗后干预组血清CA199、CA125、CEA水平均低于治疗前及对照组治疗后(P<0.05);干预组药物不良反应发生率为16.67%,对照组为36.67%,干预组低于对照组(P<0.05);治疗后干预组QOL各维度评分高于对照组及治疗前(P<0.05)。结论 与单纯化疗相比,免疫联合化疗治疗晚期NSCLC患者,能有效降低肿瘤标志物水平,改善患者免疫指标,减轻药物不良反应,提高患者疗效及生活质量。
Objective To explore the effect of immunotherapy combined with chemotherapy on lymphatic immunity and quality of life of patients with advanced non-small cell lung cancer(NSCLC),and to provide reference for further clinical treatment.Methods A total of 120 patients with NSCLC from June 2021 to June 2023 were selected and divided into observation group and control group evenly according to the method of drawing lots,control group was treated with chemotherapy,the observation group was treated with immunotherapy combined with chemotherapy,and the clinical efficacy and adverse drug reactions were compared between the two groups.Before and after treatment,immune function(CD3+ ,CD4+ ,CD8+ ),carbohydrate antigen 199(CA199),carbohydrate antigen 125(CA125),serum carcinoembryonic antigen(CEA)levels and health status questionnaire(QOL-RRB- scores)were measured.Results The total effective rate in the observation group was significantly higher than that in the control group(68.33%>41.67%,P<0.05).After treatment,the ratios of CD3+ and CD4+ in the observation group were significantly higher than those before treatment and control group after treatment,and the ratio of CD8+ was significantly lower than that before and after treatment in the control group(P<0.05).After treatment,the serum levels of CA199,CA125 and CEA in the observation group were lower than those before and after treatment in the control group(P<0.05).The incidence of adverse drug reactions was 16.67% in the observation group and 36.67% in the control group,which was significantly lower in the observation group than in the control group(P<0.05).After treatment,the QOL scores in the observation group were significantly higher than those in the control group and before treatment(P<0.05).Conclusions Compared with chemotherapy alone,immunotherapy combined with chemotherapy can effectively reduce the levels of tumor markers,improve the immune indexes of patients,reduce the adverse drug reactions,and improve the efficacy and quality of life of patients with advanced NSCLC.
实体瘤对免疫治疗应答非常有限,因此,如何有效提升肿瘤免疫治疗的疗效,已成为当前肿瘤免疫治疗领域亟待解决的关键难题与挑战。髓系来源抑制性细胞(MDSCs)的趋化募集及其所介导的肿瘤免疫逃逸机制,是制约实体瘤免疫治疗效果的核心因素之一。文章深入探讨了MDSCs的起源、表型特征、其介导肿瘤免疫逃逸的具体机制,以及当前针对MDSCs的靶向治疗策略与将MDSCs靶向疗法与肿瘤免疫治疗相结合的最新研究进展。此外,文章还系统性地分析了靶向MDSCs联合免疫治疗策略所面临的关键挑战,并据此提出了MDSCs的精准靶向策略。这一策略旨在精确激活抗肿瘤免疫反应,为癌症患者提供更为个性化、高效的治疗方案,从而开启肿瘤免疫治疗领域的新纪元,为癌症治疗策略的创新与发展贡献力量。
Solid tumors exhibit a very limited response to immunotherapy.Consequently,effectively enhancing the therapeutic efficacy of tumor immunotherapy has emerged as a critical challenge and problem that urgently needs to be addressed in tumor immunotherapy.The chemotaxis and recruitment of myeloid-derived suppressor cells(MDSCs)and the tumor immune evasionmechanisms mediated by them are one of the core factors that significantly restrict the efficacy of immunotherapy for solid tumors.In this review,we discuss the origins and phenotypic characteristics of MDSCs,the specific mechanisms by which they mediate tumor immune evasion,as well as current targeted therapeuticstrategies for MDSCs and the latest research progress in combining MDSC-targeted therapy with tumor immunotherapy.Furthermore,we have systematically analyzed the key challenges faced by the combination of MDSC-targeted and immunotherapy strategies,and accordingly proposed a precise targeting strategyfor MDSCs.This strategy aims to precisely activate anti-tumor immune responses,providing more personalized and efficienttreatment options for cancer patients,thereby opening a new era in tumor immunotherapy and contributing to the innovation anddevelopment of cancer treatment strategies.